Branching Structures in Elastic Shape Optimization

Fine scale elastic structures are widespread in nature, for instances in plants or bones, whenever stiffness and low weight are required. These patterns frequently refine towards a Dirichlet boundary to ensure an effective load transfer. The paper discusses the optimization of such supporting structures in a specific class of domain patterns in 2D, which composes of periodic and branching period transitions on subdomain facets. These investigations can be considered as a case study to display examples of optimal branching domain patterns. In explicit, a rectangular domain is decomposed into rectangular subdomains, which share facets with neighbouring subdomains or with facets which split on one side into equally sized facets of two different subdomains. On each subdomain one considers an elastic material phase with stiff elasticity coefficients and an approximate void phase with orders of magnitude softer material. For given load on the outer domain boundary, which is distributed on a prescribed fine scale pattern representing the contact area of the shape, the interior elastic phase is optimized with respect to the compliance cost. The elastic stress is supposed to be continuous on the domain and a stress based finite volume discretization is used for the optimization. If in one direction equally sized subdomains with equal adjacent subdomain topology line up, these subdomains are consider as equal copies including the enforced boundary conditions for the stress and form a locally periodic substructure. An alternating descent algorithm is employed for a discrete characteristic function describing the stiff elastic subset on the subdomains and the solution of the elastic state equation. Numerical experiments are shown for compression and shear load on the boundary of a quadratic domain.Comment: 13 pages, 6 figure

A census of cell types and paracrine interactions in colorectal cancer

In colorectal cancer, oncogenic mutations transform a hierarchically organized and homeostatic epithelium into invasive cancer tissue. To define differences in cellular composition between the normal colon and colorectal cancer, and to map potential cellular interactions between tumor cells and their microenvironment, we profiled transcriptomes of >50,000 single cells from tumors and matched normal tissues of eight colorectal cancer patients. We find that tumor formation is accompanied by changes in epithelial, immune and stromal cell compartments in all patients. In the epithelium, we identify a continuum of five tumor-specific stem cell and progenitor-like populations, and persistent multilineage differentiation. We find multiple stromal and immune cell types to be consistently expanded in tumor compared to the normal colon, including cancer-associated fibroblasts, pericytes, monocytes, macrophages and a subset of T cells. We identify epithelial tumor cells and cancer-associated fibroblasts as relevant for assigning colorectal cancer consensus molecular subtypes. Our survey of growth factors in the tumor microenvironment identifies cell types responsible for increased paracrine EGFR, MET and TGF-β signaling in tumor tissue compared to the normal colon. We show that matched colorectal cancer organoids retain cell type heterogeneity, allowing to define a distinct differentiation trajectory encompassing stem and progenitor-like tumor cells. In summary, our single-cell analyses provide insights into cell types and signals shaping colorectal cancer cell plasticity

Expression of auxin-binding protein1 during plum fruit ontogeny supports the potential role of auxin in initiating and enhancing climacteric ripening

Auxin-binding protein1 (ABP1) is an active element involved in auxin signaling and plays critical roles in auxin-mediated plant development. Here, we report the isolation and characterization of a putative sequence from Prunus salicina L., designated PslABP1. The expected protein exhibits a similar molecular structure to that of well-characterized maize-ABP1; however, PslABP1 displays more sequence polarity in the active-binding site due to substitution of some crucial amino-acid residues predicted to be involved in auxin-binding. Further, PslABP1 expression was assessed throughout fruit ontogeny to determine its role in fruit development. Comparing the expression data with the physiological aspects that characterize fruit-development stages indicates that PslABP1 up-regulation is usually associated with the signature events that are triggered in an auxin-dependent manner such as floral induction, fruit initiation, embryogenesis, and cell division and elongation. However, the diversity in PslABP1 expression profile during the ripening process of early and late plum cultivars seems to be due to the variability of endogenous auxin levels among the two cultivars, which consequently can change the levels of autocatalytic ethylene available for the fruit to co-ordinate ripening. The effect of auxin on stimulating ethylene production and in regulating PslABP1 was investigated. Our data suggest that auxin is involved in the transition of the mature green fruit into the ripening phase and in enhancing the ripening process in both auxin- and ethylene-dependent manners thereafter

Mitogen-activated protein kinase activity drives cell trajectories in colorectal cancer

In colorectal cancer, oncogenic mutations transform a hierarchically organized and homeostatic epithelium into invasive cancer tissue lacking visible organization. We sought to define transcriptional states of colorectal cancer cells and signals controlling their development by performing single-cell transcriptome analysis of tumors and matched non-cancerous tissues of twelve colorectal cancer patients. We defined patient-overarching colorectal cancer cell clusters characterized by differential activities of oncogenic signaling pathways such as mitogen-activated protein kinase and oncogenic traits such as replication stress. RNA metabolic labeling and assessment of RNA velocity in patient-derived organoids revealed developmental trajectories of colorectal cancer cells organized along a mitogen-activated protein kinase activity gradient. This was in contrast to normal colon organoid cells developing along graded Wnt activity. Experimental targeting of EGFR-BRAF-MEK in cancer organoids affected signaling and gene expression contingent on predictive KRAS/BRAF mutations and induced cell plasticity overriding default developmental trajectories. Our results highlight directional cancer cell development as a driver of non-genetic cancer cell heterogeneity and re-routing of trajectories as a response to targeted therapy

Effect of remote ischemic conditioning on atrial fibrillation and outcome after coronary artery bypass grafting (RICO-trial)

Background: Pre- and postconditioning describe mechanisms whereby short ischemic periods protect an organ against a longer period of ischemia. Interestingly, short ischemic periods of a limb, in itself harmless, may increase the ischemia tolerance of remote organs, e.g. the heart (remote conditioning, RC). Although several studies have shown reduced biomarker release by RC, a reduction of complications and improvement of patient outcome still has to be demonstrated. Atrial fibrillation (AF) is one of the most common complications after coronary artery bypass graft surgery (CABG), affecting 27-46% of patients. It is associated with increased mortality, adverse cardiovascular events, and prolonged in-hospital stay. We hypothesize that remote ischemic pre- and/or post-conditioning reduce the incidence of AF following CABG, and improve patient outcome.Methods/design: This study is a randomized, controlled, patient and investigator blinded multicenter trial. Elective CABG patients are randomized to one of the following four groups: 1) control, 2) remote ischemic preconditioning, 3) remote ischemic postconditioning, or 4) remote ischemic pre- and postconditioning. Remote conditio

Optimal sensor placement for artificialA swimmers

Natural swimmers rely for their survival on sensors that gather information from the environment and guide their actions. The spatial organization of these sensors, such as the visual fish system and lateral line, suggests evolutionary selection, but their optimality remains an open question. Here, we identify sensor configurations that enable swimmers to maximize the information gathered from their surrounding flow field. We examine two-dimensional, self-propelled and stationary swimmers that are exposed to disturbances generated by oscillating, rotating and D-shaped cylinders. We combine simulations of the Navier–Stokes equations with Bayesian experimental design to determine the optimal arrangements of shear and pressure sensors that best identify the locations of the disturbance-generating sources. We find a marked tendency for shear stress sensors to be located in the head and the tail of the swimmer, while they are absent from the midsection. In turn, we find a high density of pressure sensors in the head along with a uniform distribution along the entire body. The resulting optimal sensor arrangements resemble neuromast distributions observed in fish and provide evidence for optimality in sensor distribution for natural swimmers. Copyright © Cambridge University Press 2019

Cell type-dependent differential activation of ERK by oncogenic KRAS in colon cancer and intestinal epithelium

Oncogenic mutations in KRAS or BRAF are frequent in colorectal cancer and activate the ERK kinase. Here, we find graded ERK phosphorylation correlating with cell differentiation in patient-derived colorectal cancer organoids with and without KRAS mutations. Using reporters, single cell transcriptomics and mass cytometry, we observe cell type-specific phosphorylation of ERK in response to transgenic KRASG12V in mouse intestinal organoids, while transgenic BRAFV600E activates ERK in all cells. Quantitative network modelling from perturbation data reveals that activation of ERK is shaped by cell type-specific MEK to ERK feed forward and negative feedback signalling. We identify dual-specificity phosphatases as candidate modulators of ERK in the intestine. Furthermore, we find that oncogenic KRAS, together with β-Catenin, favours expansion of crypt cells with high ERK activity. Our experiments highlight key differences between oncogenic BRAF and KRAS in colorectal cancer and find unexpected heterogeneity in a signalling pathway with fundamental relevance for cancer therapy

The large radius human centrifuge 'A human hypergravity habitat, H ³

Over the last decades a significant body of knowledge has been gained on the adaptation of the human body going into near weightlessness conditions as well as for the re-adaptation to 1xg Earth conditions after an orbital space flight. Ground-based paradigms for microgravity simulation have been developed such as head down tilted bed rest or dry-immersion studies. In such systems adaptations of the human body to long term immobilization and increased upper-body fluid shifts bed have been studied. But could we learn something on human body adaptations to altered gravity conditions using centrifuges? How does the body adapt to a long duration (days, weeks or longer) exposure to a hypergravity environment? And, once the body has fully adapted to a hypergravity environment, how does it re-adapt going from a hypergravity condition to a relatively hypo-gravity condition of 1xg, or even going from centrifuge / hypergravity environment into a bed-rest setting? Can such transitions learn us something about the gravity transitions as a crew will experience going to Moon or Mars. Is hypergravity therefore a good model to study the effect of re-entry in gravitational environments after long duration space flight? We established a Topical Team sponsored by ESA ans supported by NASA and JAXA in which we address the issues as mentioned above. We like to address the questions for all organ systems known to change under altered gravity conditions. We will identify to which gravity levels the human body can be exposed to for longer periods of time and what protocols could be applied to address the questions at hand. We also need to identify if and how we could perform such long duration hypergravity and re-adaptation studies. Issues like ethics, safety and required technology are addressed. The final outcome of the ESA Topical Team will be a clear answer about the feasibility of long duration hypergravity, and if and how hypergravity studies can provide useful knowledge to support future space flight on the one hand and the medical issues in e.g. the ageing population with its contemporary lifestyle on the other hand (osteoporosis, cardiovascular diseases, obesity)

Comparison of Growth Responses to Auxin 1-Naphthaleneacetic Acid and the Ethylene Precursor 1-Aminocyclopropane-1-Carboxilic Acid in Maize Seedling Root

Application of 1-naphthaleneacetic acid (NAA) or 1-aminocyclopropane-1-carboxilic acid (ACC) to maize roots growing in hydroponic solution inhibited root elongation, and increased radial growth, but the responses to those treatments differed in degree. Auxin was more effective than ACC as an elongation inhibitor and root swelling promoter. Whereas NAA fully inhibited elongation and maintained swelling over 48 h, ACC inhibited elongation partially (50%) and only promoted swelling for 24 h. It is well-known that auxin, like ACC, promotes ethylene production, but similar levels of ethylene production reached by means of NAA or ACC treatments did not elicit the same response, the response being always stronger to NAA than to ACC. These results suggest that the effect of auxin on root growth is not mediated by ethylene. Elongation and swelling of roots appear to be inversely related: usually a reduction in elongation was accompanied by corresponding swelling. However, these two processes showed different sensitivities to growth regulators. After 24 h treatment with 0.5 μM NAA or 5 μM ACC, root elongation was inhibited by 90 % and 53 % respectively, but the same treatments promoted swelling by 187 % and 140 % respectively. Furthermore, 1 μM ACC was shown to promote inhibition of root elongation with-out affecting swelling. The ethylene antagonist STS (silver thiosulfate) did not affect elongation in control or NAA-treated roots, but increased ethylene production and swelling. These results indicate that longitudinal and radi